Preparation method of farnesyl-modified cysteine polypeptide

Abstract

The invention provides a preparation method of farnesyl-modified cysteine polypeptide. Cysteine protecting groups can be specifically removed at a fixed point by using 4-methoxytriphenylmethyl serving as a special cysteine protecting group under a special removal condition, while other amino acid protecting groups are not acted, and only cysteine sulfydryl is free and is used as the unique reaction locus, so that side reaction is avoided; and trans, trans-farnesyl bromide used as a farnesyl-modified raw material can be used for simply and efficiently realizing cysteine farnesyl modification in a solid-phase system, so that the aim of synthesizing a target product is achieved. The preparation method is simple in process, specified in structure, few in impurities, beneficial to purification and high in yield.

Description

technical field [0001] The invention relates to the technical field of polypeptides, in particular to a method for synthesizing farnesyl-modified cysteine ​​polypeptides. Background technique [0002] Farnesyl cysteine ​​English name farnesylcysteine ​​farnesyl cysteine ​​protein molecules (such as G protein gamma subunit) cysteine ​​residue modified by farnesyl derivatives, can help protein localization On the inner surface of the plasma membrane, 30% of human tumors are related to mutation of Ras gene and increased expression of Ras protein. Ras protein can be located inside the cell membrane only after farnesyl modification, so as to play a role in promoting growth and lead to malignant proliferation of tumor cells. The key step in this process is that under the catalysis of farnesyl transferase (FTase), the CaaX at the carboxyl end of the Ras protein (in the composition of CaaX, C is Cys, a is a hydrophobic amino acid, X is methionine and serine, etc. ) is farnesylated...

AI Technical Summary

Problems solved by technology

[0006] For this purpose, we found in the process of researching related synthesis processes that the prior art processes are relatively complicated and time-consuming

This technology mainly adopts the method of synthesizing and purifying polypeptides containing free sulfhydryl groups first, and then modifying cysteine ​​farnesyl. The active groups in other amino acids in the sequence are not protected, and other side reactions are prone to occur. This method is difficult to determine farnesyl. In addition, it is necessary to strictly control the feeding ratio to avoid impurities generated by excess raw materials; according to the reaction principle, alkaline reagents need to be added during the process to promote the reaction, and the free sulfhydryl groups in the alkaline reaction system are easily oxidized to produce Dimer impurities hinder the progress of farnesyl modification; after the reaction, post-treatment is required to extract the target product, and the process is cumbersome; more side reactions and uncertain reaction positions cause great problems for later purification and identification Difficulty, affecting final yield and structure determination

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